Using the strongest predictors (i.e., d-AMY and CRP), we established a criterion for no CR-POPF d-AMY levels less then ?350&nbsp;IU/l and CRP levels less then ?14&nbsp;mg/dl on POD3. The incidence rates of CR-POPF were 6%, 38%, and 88% in patients who fulfilled both of (n?=?149), each of (n?=?74), and none of (n?=?77) the two factors, respectively. In the internal validation cohort, the positive predictive value of CR-POPF was 89%. CONCLUSIONS A simple two-factor criterion available on POD3 after PD has a reliable predictive ability. In patients who fulfill this criterion, early drain removal is considered safe.Cytochrome P450 (CYP) enzymes play an important role in the metabolism of xenobiotics. Since they are connected to drug interactions, screening for potential inhibitors is of utmost importance in drug discovery settings. Our study provides an extensive classification model for P450-drug interactions with one of the most prominent members, the 2C9 isoenzyme. Our model involved the largest set of 45,000 molecules ever used for developing prediction models. The models are based on three different types of descriptors, (a) typical one, two and three dimensional molecular&nbsp;descriptors, (b) chemical and pharmacophore fingerprints and (c) interaction fingerprints with docking scores. Two machine learning algorithms, the boosted tree and the multilayer feedforward of resilient backpropagation network were used and compared based on their performances. The models were validated both internally and using external validation sets. The results showed that the consensus voting technique with custom probability thresholds could provide promising results even in large-scale cases without any restrictions on the applicability domain. Our best model was capable to predict the 2C9 inhibitory activity with the area under the receiver operating characteristic curve (AUC) of 0.85 and 0.84 for the internal and the external test sets, respectively. The chemical space covered with the largest available dataset has reached its limit encompassing publicly available bioactivity data for the 2C9 isoenzyme.Aging is associated with reduced liver function that may increase the risk for adverse drug reactions in older adults. We hypothesized that age-related changes to epigenetic regulation of genes involved in drug metabolism may contribute to this effect. We reviewed published epigenome-wide studies of human blood and identified the cytochrome P450 2E1 (CYP2E1) gene as a top locus exhibiting epigenetic changes with age. https://www.selleckchem.com/products/ku-0060648.html To investigate potential functional changes with age in the liver, the primary organ of drug metabolism, we obtained liver tissue from mice aged 4-32&nbsp;months from the National Institute on Aging. We assayed global DNA methylation (5-methylcytosine, 5mC), hydroxymethylation (5-hydroxymethylcytosine, 5hmC), and locus-specific 5mC and histone acetylation changes around mouse Cyp2e1. The mouse livers exhibit significant global decreases in 5mC and 5hmC with age. Furthermore, 5mC significantly increased with age at two regulatory regions of Cyp2e1 in tandem with decreases in its gene and protein expressions. H3K9ac levels also changed with age at both regulatory regions of Cyp2e1 investigated, while H3K27ac did not. To test if these epigenetic changes are associated with varying rates of drug metabolism, we assayed clearance of the CYP2E1-specific probe drug chlorzoxazone in microsome extracts from the same livers. CYP2E1 intrinsic clearance is associated with DNA methylation and H3K9ac levels at the Cyp2e1 locus but not with chronological age. This suggests that age-related epigenetic changes may influence rates of hepatic drug metabolism. In the future, epigenetic biomarkers could prove useful to guide dosing regimens in older adults.Consumption of cannabinoid-containing products is on the rise, even during pregnancy. Unfortunately, the long-term, age-related consequences of developmental cannabidiol (CBD) exposure remain largely unknown. This is a critical gap given the established Developmental Origins of Health and Disease (DOHaD) paradigm which emphasizes that stressors, like drug exposure, early in life can instigate molecular and cellular changes that ultimately lead to adverse outcomes later in life. Thus, we exposed zebrafish (Danio rerio) to varying concentrations of CBD (0.02, 0.1, 0.5&nbsp;μM) during larval development and assessed aging in both the F0 (exposed generation) and their F1 offspring 30&nbsp;months later. F0 exposure to CBD significantly increased survival (~?20%) and reduced size (wet weight and length) of female fish. While survival was increased, the age-related loss of locomotor function was unaffected and the effects on fecundity varied by sex and dose. Treatment with 0.5&nbsp;μM CBD significantly reduced sperm concentration in males, but 0.1&nbsp;μM increased egg production in females. Similar to other model systems, control aged zebrafish exhibited increased kyphosis as well as increased expression markers of senescence, and inflammation (p16ink4ab, tnfα, il1b, il6, and pparγ) in the liver. Exposure to CBD significantly reduced the expression of several of these genes in a dose-dependent manner relative to the age-matched controls. The effects of CBD on size, gene expression, and reproduction were not reproduced in the F1 generation, suggesting the influence on aging was not cross-generational. Together, our results demonstrate that developmental exposure to CBD causes significant effects on the health and longevity of zebrafish.The new decision support tool Glucosafe 2 (GS2) is based on a mathematical model of glucose and insulin dynamics, designed to assist caregivers in blood glucose control and nutrition. This study aims to assess end-user acceptance and usability of this bedside decision support tool in an adult intensive care setting. Caregivers were first trained and then invited to trial GS2 prototype on bedside computers. Data for qualitative analysis were collected through semi-structured interviews from twenty users after minimum three trial days. Most caregivers (70%) rated GS2 as convenient and believed it would help improving adherence to current guidelines (85%). Moreover, most nurses (80%) believed that GS2 would be timesaving. Nurses' risk perceptions and manual data entry emerged as central barriers to use GS2 in routine practice. Issues emerged from the caregivers were compiled into a list of 12 modifications of the GS2 prototype to increase end-user acceptance and usability. This usability study showed that GS2 was considered by ICU caregivers as helpful in daily clinical practice, allowing time-saving and better standardization of ICU patient's care.